Animal germline development and fertility rely on paralogs of general transcription factors that recruit RNA polymerase II to ensure cell type-specific gene expression. It remains unclear whether gene expression processes downstream from such paralog-based transcription is distinct from that of canonical RNA polymerase II genes. In Drosophila, the testis-specific TBP-associated factors (tTAFs) activate over a thousand spermatocyte-specific gene promoters to enable meiosis and germ cell differentiation. Here, we show that efficient termination of tTAF-activated transcription relies on testis-specific paralogs of canonical polymerase-associated factor 1 complex (PAF1C) proteins, which form a testis-specific PAF1C (tPAF). Consequently, tPAF mutants show aberrant expression of hundreds of downstream genes due to read-in transcription. Furthermore, tPAF facilitates expression of Y-linked male fertility factor genes and thus serves to maintain spermatocyte-specific gene expression. Consistently, tPAF is required for the segregation of meiotic chromosomes and male fertility. Supported by comparative in vivo protein interaction assays, we provide a mechanistic model for the functional divergence of tPAF and the PAF1C and identify transcription termination as a developmentally regulated process required for germline-specific gene expression.

中文翻译：

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种系 PAF1 旁系同源物复合物确保细胞类型特异性基因表达


动物种系发育和生育能力依赖于募集 RNA 聚合酶 II 的一般转录因子的旁系同源物，以确保细胞类型特异性基因表达。目前尚不清楚这种基于旁系同源物的转录下游的基因表达过程是否与经典 RNA 聚合酶 II 基因的基因表达过程不同。在果蝇中，睾丸特异性 TBP 相关因子 （tTAF） 激活了 1000 多个精母细胞特异性基因启动子，以实现减数分裂和生殖细胞分化。在这里，我们表明 tTAF 激活转录的有效终止依赖于经典聚合酶相关因子 1 复合物 （PAF1C） 蛋白的睾丸特异性旁系同源物，这些旁系同源物形成睾丸特异性 PAF1C （tPAF）。因此，由于读入转录，tPAF 突变体显示出数百个下游基因的异常表达。此外，tPAF 促进 Y 连锁男性生育因子基因的表达，从而有助于维持精母细胞特异性基因表达。始终需要 tPAF 来分离减数分裂染色体和男性生育能力。在比较体内蛋白质相互作用测定的支持下，我们为 tPAF 和 PAF1C 的功能分歧提供了一个机制模型，并将转录终止确定为种系特异性基因表达所需的发育调节过程。